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Association between the M129V variant allele of PRNP gene and mild temporal lobe epilepsy in women.

Specific variations in the prion protein gene (PRNP) are associated with, and prevalent in patients with intractable temporal lobe epilepsy (TLE) and influence the surgical outcome. We investigated whether or not the PRNP gene is a susceptibility gene in temporal lobe epileptic patients with mild epilepsy. We systematically screened the entire open reading frame of the PRNP gene and evaluated the genetic contribution of the functional PRNP M129V polymorphism in 289 patients with mild TLE compared with a neurologically unaffected age and sex matched control group (n=272). Statistical analysis revealed a moderate difference in the distribution at codon 129 of the PRNP gene between sporadic mild TLE patients and healthy controls (p=0.036; OR=1.30; 95% CI=1.01-1.68). Although, there was no statistically significant difference in the genotype distribution within the study groups (p=0.101), a further analysis showed that the 129V allele was highly represented only in women with TLE compared with control group (p=0.006, OR=1.632; 95%CI=1.15-2.31). This is the first publication of data that support the hypothesis that the common methionine/valine polymorphism at codon 129 of the PRNP gene may modify the susceptibility of women to mild TLE.

Adolescent↗

Diagnostic performance of 18F-FDG PET and ictal 99mTc-HMPAO SPET in pediatric temporal lobe epilepsy: quantitative analysis by statistical parametric mapping, statistical probabilistic anatomical map, and subtraction ictal SPET.

We investigated the diagnostic performance of 18F-FDG PET and ictal (99m)Tc-HMPAO SPET in pediatric temporal lobe epilepsy (TLE). Twenty-one pediatric TLE patients were enrolled in this study. Their diagnoses were confirmed by histology and post-surgical outcome (Engel class I or II). The patients' ages were 18 or younger (15+/-3 years). Of the 21 patients, 21 patients underwent 18F-FDG PET scan and 15 underwent ictal (99m)Tc-HMPAO SPET. Preoperative PET and/or ictal SPET images were reviewed by simple visual assessment and by statistical parametric mapping (SPM). Asymmetric indices (AI) were calculated using statistical probabilistic anatomical map (SPAM) on 18F-FDG PET. In nine patients who underwent both ictal and interictal SPET, SISCOM (subtraction ictal SPET coregistered to MR template) was performed. PET correctly localized epileptogenic zones in 20 of 21 (95%) by visual assessment. SPM analysis of PET correctly localized epileptogenic zones in 18 of 21 (86%). Ictal SPET correctly localized epileptogenic zones in 12 of 15 (80%) by visual assessment. SPM analysis of ictal SPET correctly localized epileptogenic zones in 12 of 15 (80%). SISCOM correctly localized 8 of 9 (89%), which was equal to that of visual assessment of ictal SPET. The AIs of the temporal lobes by PET were -15+/-8.4 in the left and 9.9+/-8.9 in the right TLE (normal control: -2.9+/-2.8), and correctly localized epileptogenic zones in all cases. As is found in adult TLE, PET and ictal SPET efficiently localized epileptogenic zones in pediatric TLE. SPM analysis of PET or ictal SPET could be used as an aid to visual assessment. Moreover, SISCOM was equal visual assessment of ictal SPET images in terms of lesion localizations.

Adolescent↗

Temporal lobe epilepsy surgery in children and adolescents: clinical characteristics and post-surgical outcome.

BACKGROUND AND PURPOSE: Temporal lobe epilepsy (TLE) encompasses 10-20% of the cases of intractable epilepsy in pediatric patients. Mesial temporal sclerosis (MTS) can still be encountered in adolescent patients, but is rare in children under 5 years of age. In this paper we report on the surgical outcome of a series of TLE patients ranging in age from 1 to 18 years at the time of operation. PATIENTS AND METHODS: Thirty-five patients (37 surgeries) with medically intractable TLE were operated upon between January 1996 and December 2002. The following variables were analyzed: age at surgery, age at epilepsy onset, history of an initial precipitating injury, etiology, seizure semiology, interictal and ictal EEG findings, surgical complications, and post-surgical seizure outcome. RESULTS: There were 68.6% females and 31.3% males, and complex partial seizures (CPS) occurred in 86.5%. The most common etiology was MTS (40%) followed by isolated cortical developmental abnormalities (22.9%). In the age group up to 5 years, cortical development abnormalities predominated, and 71% of these children had multifocal interictal EEG. Patients older than 10 years had more frequently MTS (78.6%) and focal temporal interictal EEG abnormalities. Post-surgical seizure outcome showed that 88.5% of patients were in Engel classes I and II. CONCLUSIONS: Adolescents with TLE had clinical features, electrographic findings, and seizure outcome similar to those observed in adult patients. However, younger children up to 5 years of age had distinct ictal semiology and different etiological, electrophysiological and outcome profiles, clearly suggesting that they behave as a special subgroup within the TLE.

Adolescent↗

Prognostic factors for surgery of neocortical temporal lobe epilepsy.

OBJECTIVES: In the current classification of epilepsies two forms of temporal lobe epilepsy (TLE) were included: mesial and lateral (neocortical) TLE. We aimed at identifying prognostic factors for the surgical outcome of lesional neocortical TLE. METHODS: We included consecutive patients who had undergone presurgical evaluation including ictal video-EEG and high-resolution MRI, who had TLE due to neocortical lateral epileptogenic lesions, who had a lesionectomy and who had >2-year follow-up. RESULTS: There were 29 patients who met the inclusion criteria. Twenty of them became postoperatively seizure-free. Patients' mean age was 34.8+/-9 years (range 18-52). The age at epilepsy onset was 20.1+/-8 years. We found that left-sided surgery (p=0.048) and focal cortical dysplasia (FCD) on MRI (p=0.005) were associated with non-seizure-free outcome, while lateralized/localized EEG seizure pattern (p=0.032), tumors on the MRI (p=0.013), and a favorable seizure situation at the 6-month postoperative evaluation were associated with 2-year postoperative seizure-freedom (p<0.001). Multivariate analysis indicated that the side of surgery was not an independent predictor. CONCLUSION: More than two-thirds of the patients with neocortical TLE became seizure-free postoperatively. Lateralized/localized EEG seizure pattern and tumors on the MRI were associated with postoperative seizure-freedom, while FCD were associated with a poor outcome. The 6-month postoperative outcome is a reliable predictor for the long-term outcome.

Adolescent↗

Polygenic burden and its association with baseline cognitive function and postoperative cognitive outcome in temporal lobe epilepsy.

OBJECTIVE: Demographic and disease factors are associated with cognitive deficits and postoperative cognitive declines in adults with pharmacoresistant temporal lobe epilepsy (TLE), but the role of genetic factors in cognition in TLE is not well understood. Polygenic scores (PGS) for neurological and neuropsychiatric disorders and IQ have been associated with cognition in patient and healthy populations. In this exploratory study, we examined the relationship between PGS for Alzheimer's disease (AD), depression, and IQ and cognitive outcomes in adults with TLE. METHODS: 202 adults with pharmacoresistant TLE had genotyping and completed neuropsychological evaluations as part of a presurgical work-up. A subset (n&#xa0;=&#xa0;116) underwent temporal lobe resection and returned for postoperative cognitive testing. Logistic regression was used to determine if PGS for AD, depression, and IQ predicted baseline domain-specific cognitive function and cognitive phenotypes as well as postoperative language and memory decline. RESULTS: No significant findings survived correction for multiple comparisons. Prior to correction, higher PGS for AD and depression (i.e., increased genetic risk for the disorder), but lower PGS for IQ (i.e., decreased genetic likelihood of high IQ) appeared possibly associated with baseline cognitive impairment in TLE. In comparison, higher PGS for AD and IQ appeared as possible risk factors for cognitive decline following temporal lobectomy, while the possible relationship between PGS for depression and post-operative cognitive outcome was mixed. SIGNIFICANCE: We did not observe any relationships of large effect between PGS and cognitive function or postsurgical outcome; however, results highlight several promising trends in the data that warrant future investigation in larger samples better powered to detect small genetic effects.

Adult↗

1H-MR spectroscopy: a promising method in distinguishing subgroups in temporal lobe epilepsy?

Proton MR spectroscopy offers an additional noninvasive method of supporting focus lateralization in patients with intractable temporal lobe epilepsy. In this study involving 57 patients, the ability of multivoxel 1H-MRS to differentiate between mesial and lateral TLE was investigated in addition to its ability to lateralize the epileptogenic focus. Temporal lobe epilepsy (TLE) was classified into mesiobasal or lateral temporal lobe epilepsy according to the results of preoperative diagnostics including neurological and neuropsychological examinations, video-EEG monitoring and high resolution MRI. 1H-MR-spectroscopy (1H-MRS) showed that pathological changes in the mesial temporal lobes indicate a predominance in different parts of the ipsilateral temporal lobe (hippocampal and parahippocampal areas) correlating to the clinically defined groups. In addition, mesiobasal TLE tends to have higher concomitant contralateral abnormalities. Our results reveal that 1H-MRS is able to distinguish between mesiobasal and lateral pathologies in patients with TLE and represents a useful tool for noninvasive TLE classification.

Adult↗

Recognition and identification of famous faces in patients with unilateral temporal lobe epilepsy.

We examined the performance of 21 patients with unilateral temporal lobe epilepsy (TLE) and hippocampal damage (10 lefts, and 11 rights) and 10 age-matched controls on the recognition and identification (name and occupation) of well-known faces. Famous face stimuli were selected from four time periods; 1970s, 1980s, 1990-1994, and 1995-1996. Differential patterns of performance were observed for the left and right TLE group across distinct face processing components. The left TLE group showed a selective impairment in naming famous faces while they performed similar to the controls in face recognition and semantic identification (i.e. occupation). In contrast, the right TLE group was impaired across all components of face memory; face recognition, semantic identification, and face naming. Face naming impairment in the left TLE group was characterized by a temporal gradient with better naming performance for famous faces from more distant time periods. Findings are discussed in terms of the role of the temporal lobe system for the acquisition, retention, and retrieval of face semantic networks, and the differential effects of lateralized temporal lobe lesions in this process.

Adult↗

Pharmacokinetics of thrombin-like enzyme from venom of Agkistrodon halys ussuriensis Emelianov determined by ELISA in the rat.

A thrombin-like enzyme (TLE) was separated and purified from the venom of a northeast Chinese snake Agkistrodon halys ussuriensis Emelianov. Experiments were performed in rats to determine the pharmacokinetic parameters following an intravenous (i.v.) or a subcutaneous (s.c.) injection of the thrombin-like enzyme. The plasma levels of TLE were estimated by enzyme-linked immunosorbent assay. The method exhibited high reproducibility and accuracy in correlating optical densities with TLE concentrations (0.2-30 ng ml(-1), r=0.99). The plasma concentration-time course after i.v. administration of 50 microg kg(-1) TLE was well fitted by a two-compartment open model. The half-life of the alpha-phase was 18.0+/-3.2 min, and that of the beta-phase 3.9+/-0.7h. The apparent volume of distribution was 1.8+/-0.5l kg(-1), and clearance was 5.4+/-0.5 ml min(-1) kg(-1). When the TLE was injected s.c. at a dose of 0.75 mg kg(-1), the changes in plasma concentration were best described by a two-compartment model with a first-order absorption. The maximal plasma level of 51+/-2.7 ng ml(-1) was reached at 5.2+/-0.5h. The absorption rate constant was 0.3+/-0.03 h(-1). The area under the plasma concentration-time curve (AUC) was 2.8+/-0.8 microg h(-1) ml(-1).

Agkistrodon↗

Hippocampal neuron damage in human epilepsy: Meyer's hypothesis revisited.

Whether hippocampal neuron loss and/or hippocampal sclerosis is the 'cause' or 'consequence' of seizures has been a fundamental question in human epilepsy studies for over a century. To address this question, this study examined hippocampal specimens from temporal lobe epilepsy patients (TLE; n = 572) and those with extra-temporal seizures and pathologies (n = 73) for qualitative signs of hippocampal sclerosis and quantitative neuron loss using cell counting techniques. Patients were additionally classified based on pathological substrate, and history of an initial precipitating injury (IPI). Results showed that: (1) Hippocampal sclerosis was strongly linked with an IPI in both TLE and extra-temporal seizure patients. (2) In TLE cases, IPIs showed an early age preference and often involved seizures, but IPIs were not age dependent and older IPI cases showed sclerosis that was indistinguishable from younger IPI patients. (3) In TLE patients, longer seizure durations were associated with decreased neuronal densities in all hippocampal subfields. The decrease was independent of the neuron loss linked with IPIs, it occurred in all pathological groups, it occurred over 30 years or more, and was not a consequence of aging. (4) Intractable seizures in the young human hippocampus were not associated with neuronal damage, but were linked with decreased postnatal granule cell development and aberrant axon sprouting. These results support the concept that hippocampal sclerosis is likely an acquired pathology, and most of the neuronal loss occurs with the IPI. In addition, there is progressive hippocampal damage from intractable TLE regardless of pathology. Hence, hippocampal neuron loss can be the 'consequence' of repeated limbic seizures over 30 years or more, but is unlikely to 'cause' hippocampal sclerosis unless there is also an IPI.

Adolescent↗

The neurodevelopmental impact of childhood onset temporal lobe epilepsy on brain structure and function and the risk of progressive cognitive effects.

The purpose of this study is to explore the possibility of progressive neuropsychological decline in chronic temporal lobe epilepsy (TLE) and determine how this vulnerability may be associated with the neurodevelopmental impact of the disorder. 53 patients with TLE and 62 healthy controls underwent quantitative MRI volumetric imaging of total brain tissue and hippocampal volumes as well as assessment of intelligence and memory function. In addition to reduced hippocampal volume, childhood onset (< 14 years) but not adult onset TLE was associated with significantly reduced total brain tissue that was generalized in nature and extended into extratemporal regions. In addition to this adverse impact on brain structure, there was significantly reduced intellectual status as well as memory function in childhood onset TLE patients, consistent with the generalized nature of the MRI volumetric abnormalities. Finally, cross-sectional correlational analyses indicated that increasing duration of epilepsy in childhood onset patients was associated with declining performance across both intellectual and memory measures, suggestive of progressive cognitive effects. We propose that childhood onset TLE is associated with an adverse neurodevelopmental impact on brain structure and function which represents an early acquired vulnerability, effectively reducing cerebral reserve, placing patients at risk for progressive cognitive decline in the context of chronic and unremitting epilepsy.

Age of Onset↗

Childhood febrile convulsions--which factors determine the subsequent epilepsy syndrome? A retrospective study.

To analyze the spectrum of epilepsy syndromes which follow childhood febrile convulsions (FC) and to examine whether retrospective analysis of clinical features of the FC enables discrimination of patients who develop temporal lobe epilepsy (TLE) from those who develop generalized epilepsy (GE). One hundred and thirteen patients with epilepsy and antecedent FC were retrospectively analyzed. We inquired in detail about the clinical characteristics of FC (age, duration, number, focal symptoms) as well as family history, birth history, neurological status, and psychomotor development before onset of FC. Forty five (39.8%) patients had TLE, 41 (36.6%) GE, and 27 (23.9%) had extratemporal epilepsy (ETE). Patients with TLE had a significantly longer duration of FC (P< or =0.001), more often focal features (P< or =0.001), and febrile status epilepticus (P< or =0.001) than patients with GE. Age at FC, Number of FC, family history, birth history and neurological status at FC did not differ between groups. A stepwise discriminant model allowed correct assignment after cross validation in 84.2% to TLE and in 100% to GE. A broad spectrum of epilepsy syndromes follow FC. We found a strong association of prolonged and focal FC with later development of TLE. Short generalized FC were associated with GE.

Adolescent↗

Thalamic glucose metabolism in temporal lobe epilepsy measured with 18F-FDG positron emission tomography (PET).

Thalamic glucose metabolism has been studied in 24 patients suffering from temporal lobe epilepsy (TLE) using interictal 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET). A total of 17 patients had a unilateral TL seizure onset, 11 of these patients had a mesial temporal lobe epilepsy syndrome (MTLE), with mesial gliosis and a mesial TL seizure origin. Three patients had a lateral TL seizure origin, and 3 patients had mesial TL tumors. Bilateral TLE was assumed in 7 patients. Only in the patient group with MTLE (n = 11), the ipsilateral thalamic glucose uptake showed a statistically significant lower value when compared to the thalamus of the contralateral side (Wilcoxon paired sign test, P = 0.012). There was a more pronounced hypometabolism in right TLE compared to left TLE. A 'hypersynchronous seizure onset pattern' in ictal EEG was only seen in 6 (26%) patients (1 patient with bilateral, 5 with unilateral TLE). No correlation existed between the thalamic, temporal glucose metabolism and the 'hypersynchronous seizure onset pattern'.

Adult↗

Lateralizing value of the Wada memory test in non-Western patients with temporal lobe epilepsy.

The Wada memory test measures a psychological construct (i.e. memory), which is widely acknowledged to be under the influence of a vast array of moderating variables including culture. Thus, the lateralizing value of the Wada memory test for epileptogenic foci may potentially differ for Western versus non-Western patients with temporal lobe epilepsy (TLE). In the present study, the lateralizing value of the Wada memory test was investigated in 17 Korean patients with medically intractable TLE who were post-operatively seizure-free. The Wada memory stimuli were composed of eight drawings of common objects, animals, and fruits. A clinical criterion of at least 2 points difference between left and right injections correctly classified 14 patients (82%) into left and right TLE groups, with only one patient (6%) falsely classified. This diagnostic accuracy is at least as high as that reported for Western TLE patients. These results indicate that whatever culture-specific factors Korean TLE patients may bring to the Wada memory test, they do not significantly reduce the lateralizing value of the test.

Adult↗

Auditory naming and temporal lobe epilepsy.

Patients with left (i.e. language-dominant) temporal lobe epilepsy (TLE) typically report word finding difficulties. However, these deficits are not reliably detected with traditional visual object naming tests. We administered both visual and auditory naming tests to left and right TLE patients and normal controls. We hypothesized that an auditory naming test might be more sensitive since it better simulates the conditions under which word finding problems occur in daily living. The left TLE group obtained significantly lower scores than other groups on auditory naming, whereas their performance on visual naming was indistinguishable from that of right TLE patients and normals. Furthermore, whereas cut-off scores on the auditory naming task predicted seizure focus laterality in 85% of patients, performance on the visual naming task predicted laterality in only 60% of patients. These findings suggest that compared with visual naming, as assessed in the present study, auditory naming may more accurately characterize and lateralize TLE-associated language dysfunction. These results also propose a more complex understanding of word retrieval that incorporates modality and contextual information.

Acoustic Stimulation↗

Temporal lobe epilepsy with sensory aura: interictal glucose hypometabolism.

Patients with mesial temporal lobe epilepsy (mTLE) exhibit marked depressions of the regional cerebral glucose metabolism (rCMRGlu) in the mesiotemporal region. We hypothesised that patients with temporal lobe epilepsy (TLE) who have a bilateral somatosensory or acoustic ( = temporolateral/SII-) aura can be differentiated from mTLE by rCMRGlu depressions primarily involving temporo-perisylvian locations. We therefore used this ictal semiology as a clinical criterion to define a subgroup of such patients and measured the rCMRGlu in 16 patients with TLE as evident from interictal and ictal EEG-video monitoring. Clinically, they presented with medically refractory complex partial seizures and were subjected to presurgical evaluation. The pattern of the interictal rCMRGlu in the TLE patients was different from that observed in patients with mTLE and showed significant depressions ipsilateral to the epileptic focus in mesial temporal and lateral temporal regions but spared the thalamus. The neocortical metabolic depressions were spatially more extended in right than in left TLE patients. Magnetic resonance images (MRI) were either normal (n = 5) or revealed unilateral or bilateral hippocampal atrophy/sclerosis (n = 7), or temporal or extratemporal focal cortical dysplasia (n = 4). The selected TLE patients presented here comprise a heterogeneous group showing most pronounced metabolic depressions in the lateral temporal cortex. Thus, our data suggest that non-invasive metabolic imaging can assist in identifying the neocortical symptomatogenic zone in putative temporo-perisylvian lobe epilepsy.

Abdomen↗

Characterization of neocortical and hippocampal synaptosomes from temporal lobe epilepsy patients.

To investigate epilepsy-associated changes in the presynaptic terminal, we isolated and characterized synaptosomes from biopsies resected during surgical treatment of drug-resistant temporal lobe epilepsy (TLE) patients. Our main findings are: (1) The yield of synaptosomal protein from biopsies of epilepsy patients was about 25% of that from rat brain. Synaptosomal preparations were essentially free of glial contaminations. (2) Synaptosomes from TLE patients and naive rat brain, quickly responded to K(+)-depolarization with a 70% increase in intrasynaptosomal Ca(2+) ([Ca(2+)](i)), and a 40% increase in B-50/GAP-43 phosphorylation. (3) Neocortical and hippocampal synaptosomes from TLE patients contained 20-50% of the glutamate and gamma-aminobutyric acid (GABA) contents of rat cortical synaptosomes. (4) Although the absolute amount of glutamate and GABA released under basal conditions from neocortical synaptosomes of TLE patients was lower than from rat synaptosomes, basal release expressed as percentage of total content was higher (16.4% and 17.3%, respectively) than in rat (11.5% and 9. 9%, respectively). (5) Depolarization-induced glutamate and GABA release from neocortical synaptosomes from TLE patients was smaller than from rat synaptosomes (3.9% and 13.0% vs. 21.9% and 25.0%, respectively). (6) Analysis of breakdown of glial fibrillary acid protein (GFAP) indicates that resection time (anoxic period during the operation) is a critical parameter for the quality of the synaptosomes. We conclude that highly pure and viable synaptosomes can be isolated even from highly sclerotic human epileptic tissue. Our data show that in studies on human synaptosomes it is of critical importance to distinguish methodological (i.e., resection time) from pathology-related abnormalities.

Adult↗

Magnetoencephalographic yield of interictal spikes in temporal lobe epilepsy. Comparison with scalp EEG recordings.

To compare magnetoencephalography (MEG) with scalp electroencephalography (EEG) in the detection of interictal spikes in temporal lobe epilepsy (TLE), we simultaneously recorded MEG and scalp EEG with a whole-scalp neuromagnetometer in 46 TLE patients. We visually searched interictal spikes on MEG and EEG channels and classified them into three types according to their presentation on MEG alone (M-spikes), EEG alone (E-spikes), or concomitantly on both modalities (M/E-spikes). The M-spikes and M/E-spikes were localized with MEG equivalent current dipole modeling. We analyzed the relative contribution of MEG and EEG in the overall yield of spike detection and also compared M-spikes with M/E-spikes in terms of dipole locations and strengths. During the 30- to 40-min MEG recordings, interictal spikes were obtained in 36 (78.3%) of the 46 patients. Among the 36 patients, most spikes were M/E-spikes (68.3%), some were M-spikes (22.1%), and some were E-spikes (9.7%). In comparison with EEG, MEG gave better spike yield in patients with lateral TLE. Sources of M/E- and M-spikes were situated in the same anatomical regions, whereas the average dipole strength was larger for M/E- than M-spikes. In conclusion, some interictal spikes appeared selectively on either MEG or EEG channels in TLE patients although more spikes were simultaneously identified on both modalities. Thus, simultaneous MEG and EEG recordings help to enhance spike detection. Identification of M-spikes would offer important localization of irritative foci, especially in patients with lateral TLE.

Adolescent↗

Depression and anxiety before and after temporal lobe epilepsy surgery.

PURPOSE: To examine the course of depression and anxiety in patients with temporal lobe epilepsy (TLE) treated with epilepsy surgery (and anticonvulsant drugs) or medical means alone. METHODS: Of 94 TLE patients evaluated for epilepsy surgery, 76 underwent a resective procedure, 18 continued on medical treatment alone. Depression (Beck Depression Inventory (BDI)) and anxiety scores (Self-Rating Anxiety Scale (SRAS)) were examined during presurgical evaluation (T1) and after a mean of 16 months (T2), or 12 months after surgery. Depression and anxiety scores were related to type of intervention, underlying epileptogenic lesion, change of seizure control and anticonvulsant therapy. RESULTS: At T1, depression and anxiety scores were higher in patients with TLE than scores in published normal populations. At T2, depression but not anxiety scores were significantly lower than at T1. Change of depression scores interacted with improvements of seizure control. CONCLUSIONS: Evidence of depression and anxiety is commonly found in patients with TLE. Depression improves not because of epilepsy surgery per se, but because of improved seizure control. This is more commonly achieved by surgery than medical treatment. The results are consistent with the hypothesis that depression in TLE is caused by pathological epileptic activity rather than a fixed structural defect.

Adult↗